1. Field of the Invention
The teachings are directed to a medical device having a drug-retaining coating that at least substantially delays the initial elution of a drug for a time effective at forming a functional endothelium over a surface of the medical device.
2. Description of the Related Art
Polymers and other materials have been utilized to control the release of drugs from coatings, capsules, tablets, and other platforms in the medical device industry. One of the challenges with drug elution into a biological system is the dosage and timing curve after deployment into such system.
Local delivery of agents is often preferred over systemic delivery of agents, particularly where high systemic doses are necessary to achieve an effect at a particular site within a subject, because high systemic doses of agents can often create adverse effects within the subject. One proposed method of local delivery includes coating the surface of a medical article with a polymeric carrier and attaching an agent to, or blending the agent with, the polymeric carrier. Some of the currently desired polymeric materials such as, for example, the poly(hydroxyalkanoates) are biodegradable.
In the cardiovascular stent field, an exhaustive number of configurations of drug eluting stents have been investigated to control the deposition of cellular material onto recently-deployed stent prostheses. It has been discovered over time that bare metal stents are likely to become covered with platelets, leukocytes, endothelial cells, smooth muscle cells (“SMC”), and fibrous tissue matrix after deployment within the cardiovascular system, such as in a cardiac artery. The platelet deposition, leukocyte recruitment, SMC proliferation, and matrix deposition responses have caused detrimental physiological effects within such a system such as compromised blood flow due to slow clogging of the stent (restenosis). In attempts to retain patency, or prevent restenosis, through such stent structures after deployment, various companies have developed composite stent prostheses comprising, in various forms, a bare metal stent coated with a drug-containing coating, the drug being one configured to prevent, at least transiently, the proliferation of tissues which may lead to partial or complete restenosis of the stent. Problems of thrombus formation and development of hyperproliferative tissue remain of great concern to those skilled in the art.
One problem is that an initial burst of drug, such as an anti-proliferative drug used to prevent restenosis, has caused unwanted biological responses, such as an inhibition of development of functional endothelium. The lack of functional endothelialization can render the stent vulnerable to blood clots (thrombosis) and can require that the patient remain on aggressive anti-thrombogenic drug therapy to prevent blood clots. As such, one of skill would appreciate a coating system that facilitates formation of a functional endothelium, soon after implantation, as a source of thrombomodulin, a natural anti-clotting protein. Another problem is the development of hyperproliferative tissue. Avoiding the use of an anti-proliferative may provide the functional endothelium but, unfortunately, the formation of excess hyperproliferative tissue can result in a potentially harmful restenosis in vascular applications, for example, a condition including an excessive deposition and/or proliferation of tissue in the region of the implant. Finally, the anti-proliferative drug can also be lost to the blood stream or surrounding causing side effects if released too soon and there would be lack of drug to be effective at a later time point after implantation when unwanted tissue hyperproliferation occurs. Since these issues are not isolated to cardiovascular drug-eluting stents, one of skill in the art of implantable medical devices would appreciate having such an enhanced control over drug elution for a variety of applications, including simple ingested, injected or implanted medications, and coated prosthetic platforms, such as stents, screws, pellets, and the like.
Accordingly, there is a need for coatings (i) that have sufficient mechanical properties for applications that can benefit from biodegradable polymers, (ii) that can release agents after formation of a functional endothelium that provides a localized source of thrombomodulin, (iii) that can be designed to have a predetermined release rate and absorption rate to inhibit the formation of hyperproliferative tissue; and (iv) that can be combined with agents that are not only bioactive and/or biobeneficial but also control a physical property and/or a mechanical property of a medical article formed from the polymer.